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1.
Objective
In Parkinson''s disease (PD), commonly reported risk factors for malnutrition in other populations commonly occur. Few studies have explored which of these factors are of particular importance in malnutrition in PD. The aim was to identify the determinants of nutritional status in people with Parkinson''s disease (PWP).Methods
Community-dwelling PWP (>18 years) were recruited (n = 125; 73M/52F; Mdn 70 years). Self-report assessments included Beck''s Depression Inventory (BDI), Spielberger Trait Anxiety Inventory (STAI), Scales for Outcomes in Parkinson''s disease – Autonomic (SCOPA-AUT), Modified Constipation Assessment Scale (MCAS) and Freezing of Gait Questionnaire (FOG-Q). Information about age, PD duration, medications, co-morbid conditions and living situation was obtained. Addenbrooke''s Cognitive Examination (ACE-R), Unified Parkinson''s Disease Rating Scale (UPDRS) II and UPDRS III were performed. Nutritional status was assessed using the Subjective Global Assessment (SGA) as part of the scored Patient-Generated Subjective Global Assessment (PG-SGA).Results
Nineteen (15%) were malnourished (SGA-B). Median PG-SGA score was 3. More of the malnourished were elderly (84% vs. 71%) and had more severe disease (H&Y: 21% vs. 5%). UPDRS II and UPDRS III scores and levodopa equivalent daily dose (LEDD)/body weight(mg/kg) were significantly higher in the malnourished (Mdn 18 vs. 15; 20 vs. 15; 10.1 vs. 7.6 respectively). Regression analyses revealed older age at diagnosis, higher LEDD/body weight (mg/kg), greater UPDRS III score, lower STAI score and higher BDI score as significant predictors of malnutrition (SGA-B). Living alone and higher BDI and UPDRS III scores were significant predictors of a higher log-adjusted PG-SGA score.Conclusions
In this sample of PWP, the rate of malnutrition was higher than that previously reported in the general community. Nutrition screening should occur regularly in those with more severe disease and depression. Community support should be provided to PWP living alone. Dopaminergic medication should be reviewed with body weight changes. 相似文献2.
Yating Deng Jianqing Ye Qing Luo Zhikun Huang Yiping Peng Guoliang Xiong Yang Guo Hong Jiang Junming Li 《PloS one》2016,11(4)
Tuberculosis remains a global health problem caused by infection with Mycobacterium tuberculosis. Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present in the peripheral blood mononuclear cell (PBMC) fraction in humans. This population of granulocytes, termed low-density granulocytes (LDGs), was reported to be elevated and associated with disease activity or severity in a number of different conditions including SLE, asthma and HIV infection. However, both the frequency and clinical significance of LDGs associated with tuberculosis are unclear. Here we determined LDG levels and made comparisons between subjects with active pulmonary tuberculosis (PTB) and healthy controls, between PTB patients with mild-to-moderate disease and patients with advanced disease, and among PTB patients following anti-tuberculous therapy of varying durations. The direct correlation between M. tuberculosis infection and LDG levels was confirmed by in vitro infection of whole peripheral blood and isolated granulocytes with mycobacteria. Our results demonstrated that PBMCs in PTB patients contained significantly elevated percentages of LDGs compared with control subjects. LDGs in tuberculosis expressed higher levels of activation markers compared to normal-density granulocytes (NDGs). M. tuberculosis induced the generation of LDGs in both whole blood and isolated NDGs from control subjects, which suggests that LDGs associated with M. tuberculosis infection are likely to originate from in situ activation. Furthermore, our results revealed that the frequency of LDGs is associated with the severity of tuberculosis. 相似文献
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4.
Brendan K. Podell David F. Ackart Natalie M. Kirk Sarah P. Eck Christopher Bell Randall J. Basaraba 《PloS one》2012,7(10)
Hyperglycemia, the diagnostic feature of diabetes also occurs in non-diabetics associated with chronic inflammation and systemic insulin resistance. Since the increased risk of active TB in diabetics has been linked to the severity and duration of hyperglycemia, we investigated what effect diet-induced hyperglycemia had on the severity of Mycobacterium tuberculosis (Mtb) infection in non-diabetic guinea pigs. Post-prandial hyperglycemia was induced in guinea pigs on normal chow by feeding a 40% sucrose solution daily or water as a carrier control. Sucrose feeding was initiated on the day of aerosol exposure to the H37Rv strain of Mtb and continued for 30 or 60 days of infection. Despite more severe hyperglycemia in sucrose-fed animals on day 30, there was no significant difference in lung bacterial or lesion burden until day 60. However the higher spleen and lymph node bacterial and lesion burden at day 30 indicated earlier and more severe extrapulmonary TB in sucrose-fed animals. In both sucrose- and water-fed animals, serum free fatty acids, important mediators of insulin resistance, were increased by day 30 and remained elevated until day 60 of infection. Hyperglycemia mediated by Mtb infection resulted in accumulation of advanced glycation end products (AGEs) in lung granulomas, which was exacerbated by sucrose feeding. However, tissue and serum AGEs were elevated in both sucrose and water-fed guinea pigs by day 60. These data indicate that Mtb infection alone induces insulin resistance and chronic hyperglycemia, which is exacerbated by sucrose feeding. Moreover, Mtb infection alone resulted in the accumulation tissue and serum AGEs, which are also central to the pathogenesis of diabetes and diabetic complications. The exacerbation of insulin resistance and hyperglycemia by Mtb infection alone may explain why TB is more severe in diabetics with poorly controlled hyperglycemia compared to non-diabetics and patients with properly controlled blood glucose levels. 相似文献
5.
Hai Gao Raviteja Reddy Guddeti Yasushi Matsuzawa Li-Ping Liu Li-Xiao Su Duo Guo Shao-Ping Nie Jie Du Ming Zhang 《PloS one》2015,10(5)
MethodsA total of 195 consecutive subjects who underwent coronary angiography for chest pain evaluation were enrolled in this study. In CAD patients severity of coronary lesions was assessed by the number of diseased vessels and the Synergy between PCI with Taxus and Cardiac surgery score (SYNTAX score). Plasma levels of miRNA-145 were quantified by real-time quantitative polymerase chain reaction test, and logarithmic transformation of miRNA-145 levels (Ln_miRNA-145) was used for analyses due to its skewed distribution.ResultsOf the 195 total subjects 167 patients were diagnosed as having CAD. Ln_miRNA-145 was significantly lower in CAD patients compared with the non-CAD group (-6.11±0.92 vs. -5.06±1.25; p <0.001). In multivariable linear regression analyses CAD was significantly associated with lower Ln_miRNA-145 (Estimate, -0.50; standard error (SE), 0.11; p <0.0001). Furthermore, among CAD patients, three-vessel disease, higher SYNTAX scores and STEMI were significantly associated with lower Ln_miRNA-145 ([Estimate, -0.40; SE, 0.07; p <0.0001]; [Estimate, -0.02, SE, 0.10; p = 0.005] and [Estimate, -0.35, SE, 0.10; p <0.001] respectively).ConclusionsLower plasma levels of miRNA-145 were significantly associated with the presence as well as severity of CAD. As a potential biomarker for CAD, plasma miRNA-145 may be useful in predicting CAD and its severity in patients presenting with chest pain. 相似文献
6.
Background
Primary defects in host immune responses have been hypothesised to contribute towards an inability of subjects with cystic fibrosis (CF) to effectively clear pulmonary infections. Innate T-lymphocytes provide rapid pathogen-specific responses prior to the development of classical MHC class I and II restricted T-cell responses and are essential to the initial control of pulmonary infection. We aimed to examine the relationship between peripheral blood lymphocyte phenotype and clinical outcomes in adults with CF.Methods
We studied 41 subjects with CF and 22, age matched, non-smoking healthy control subjects. Lymphocytes were extracted from peripheral blood samples and phenotyped by flow-cytometry. Lymphocyte phenotype was correlated with sputum microbiology and clinical parameters.Results
In comparison to healthy control subjects, mucosal associated invariant T (MAIT)-lymphocytes were significantly reduced in the peripheral blood of subjects with CF (1.1% versus 2.0% of T-lymphocytes, P = 0.002). MAIT cell concentration was lowest in CF subjects infected with P. aeruginosa and in subjects receiving treatment for a pulmonary exacerbation. Furthermore a reduced MAIT cell concentration correlated with severity of lung disease.Conclusion
Reduced numbers of MAIT cells in subjects with CF were associated with P. aeruginosa pulmonary infection, pulmonary exacerbations and more severe lung disease. These findings provide the impetus for future studies examining the utility of MAIT cells in immunotherapies and vaccine development. Longitudinal studies of MAIT cells as biomarkers of CF pulmonary infection are awaited. 相似文献7.
8.
Junning Wang Weijuan Guo Hong Du Haitao Yu Wei Jiang Ting Zhu Xuefan Bai Pingzhong Wang 《PloS one》2014,9(11)
Background
Hantaan virus is a major zoonotic pathogen that causesing hemorrhagic fever with renal syndrome (HFRS). Although HFRS pathogenesis has not been entirely elucidated, the importance of host-related immune responses in HFRS pathogenesis has been widely recognized. CD163, a monocyte and macrophage-specific scavenger receptor that plays a vital function in the hosts can reduce inflammation, is shed during activation as soluble CD163 (sCD163). The aim of this study was to investigate the pathological significance of sCD163 in patients with HFRS.Methods
Blood samples were collected from 81 hospitalized patients in Tangdu Hospital from October 2011 to January 2014 and from 15 healthy controls. The sCD163 plasma levels were measured using a sandwich ELISA, and the relationship between sCD163 and disease severity was analyzed. Furthermore, CD163 expression in 3 monocytes subset was analyzed by flow cytometry.Results
The results demonstrated that sCD163 plasma levels during the HFRS acute phase were significantly higher in patients than during the convalescent stage and the levels in the healthy controls (P<0.0001). The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001). A Spearman correlation analysis indicated that the sCD163 levels were positively correlated with white blood cell, serum creatine, blood urea nitrogen levels, while they were negatively correlated with blood platelet levels in the HFRS patients. The monocyte subsets were significantly altered during the acute stage. Though the CD163 expression levels within the monocyte subsets were increased during the acute stage, the highest CD163 expression level was observed in the CD14++CD16+ monocytes when compared with the other monocyte subsets.Conclusion
sCD163 may be correlated with disease severity and the disease progression in HFRS patients; however, the underlying mechanisms should be explored further. 相似文献9.
Elisabeth Astrup Jeshina Janardhanan Kari Otterdal Thor Ueland John A. J. Prakash Tove Lekva ?ystein A. Strand O. C. Abraham Kurien Thomas Jan Kristian Dam?s Prasad Mathews Dilip Mathai P?l Aukrust George M. Varghese 《PLoS neglected tropical diseases》2014,8(2)
Background
Scrub typhus, caused by Orientia tsutsugamushi, is endemic in the Asia-Pacific region. Mortality is high if untreated, and even with treatment as high as 10–20%, further knowledge of the immune response during scrub typhus is needed. The current study was aimed at comparing plasma levels of a variety of inflammatory mediators in scrub typhus patients and controls in South India in order to map the broader cytokine profile and their relation to disease severity and clinical outcome.Methodology/Principal Findings
We examined plasma levels of several cytokines in scrub typhus patients (n = 129) compared to healthy controls (n = 31) and infectious disease controls (n = 31), both in the acute phase and after recovery, by multiplex technology and enzyme immunoassays. Scrub typhus patients were characterized by marked changes in the cytokine network during the acute phase, differing not only from healthy controls but also from infectious disease controls. While most of the inflammatory markers were raised in scrub typhus, platelet-derived mediators such as RANTES were markedly decreased, probably reflecting enhanced platelet activation. Some of the inflammatory markers, including various chemokines (e.g., interleukin-8, monocyte chemoattractant peptide-1 and macrophage inflammatory protein-1β) and downstream markers of inflammation (e.g., C-reactive protein and pentraxin-3), were also associated with disease severity and mortality during follow-up, with a particular strong association with interleukin-8.Conclusions/Significance
Our findings suggest that scrub typhus is characterized by a certain cytokine profile that includes dysregulated levels of a wide range of mediators, and that this enhanced inflammation could contribute to disease severity and clinical outcome. 相似文献10.
Kemajittra Jenjaroen Suchintana Chumseng Manutsanun Sumonwiriya Pitchayanant Ariyaprasert Narisara Chantratita Piyanate Sunyakumthorn Maliwan Hongsuwan Vanaporn Wuthiekanun Helen A. Fletcher Prapit Teparrukkul Direk Limmathurotsakul Nicholas P. J. Day Susanna J. Dunachie 《PLoS neglected tropical diseases》2015,9(10)
Background
Melioidosis is an increasingly recognised cause of sepsis and death across South East Asia and Northern Australia, caused by the bacterium Burkholderia pseudomallei. Risk factors include diabetes, alcoholism and renal disease, and a vaccine targeting at-risk populations is urgently required. A better understanding of the protective immune response in naturally infected patients is essential for vaccine design.Methods
We conducted a longitudinal clinical and immunological study of 200 patients with melioidosis on admission, 12 weeks (n = 113) and 52 weeks (n = 65) later. Responses to whole killed B. pseudomallei were measured in peripheral blood mononuclear cells (PBMC) by interferon-gamma (IFN-γ) ELIspot assay and flow cytometry and compared to those of control subjects in the region with diabetes (n = 45) and without diabetes (n = 43).Results
We demonstrated strong CD4+ and CD8+ responses to B. pseudomallei during acute disease, 12 weeks and 52 weeks later. 28-day mortality was 26% for melioidosis patients, and B. pseudomallei-specific cellular responses in fatal cases (mean 98 IFN-γ cells per million PBMC) were significantly lower than those in the survivors (mean 142 IFN-γ cells per million PBMC) in a multivariable logistic regression model (P = 0.01). A J-shaped curve association between circulating neutrophil count and mortality was seen with an optimal count of 4000 to 8000 neutrophils/μl.Melioidosis patients with known diabetes had poor diabetic control (median glycated haemoglobin HbA1c 10.2%, interquartile range 9.2–13.1) and showed a stunted B. pseudomallei-specific cellular response during acute illness compared to those without diabetes.Conclusions
The results demonstrate the role of both CD4+ and CD8+ T-cells in protection against melioidosis, and an interaction between diabetes and cellular responses. This supports development of vaccine strategies that induce strong T-cell responses for the control of intracellular pathogens such as B. pseudomallei. 相似文献11.
Coincident Pre-Diabetes Is Associated with Dysregulated Cytokine Responses in Pulmonary Tuberculosis
Nathella Pavan Kumar Vaithilingam V. Banurekha Dina Nair Rathinam Sridhar Hardy Kornfeld Thomas B. Nutman Subash Babu 《PloS one》2014,9(11)
Background
Cytokines play an important role in the pathogenesis of pulmonary tuberculosis (PTB) - Type 2 diabetes mellitus co-morbidity. However, the cytokine interactions that characterize PTB coincident with pre-diabetes (PDM) are not known.Methods
To identify the influence of coincident PDM on cytokine levels in PTB, we examined circulating levels of a panel of cytokines in the plasma of individuals with TB-PDM and compared them with those without PDM (TB-NDM).Results
TB-PDM is characterized by elevated circulating levels of Type 1 (IFNγ, TNFα and IL-2), Type 17 (IL-17A and IL-17F) and other pro-inflammatory (IL-1β, IFNβ and GM-CSF) cytokines. TB-PDM is also characterized by increased systemic levels of Type 2 (IL-5) and regulatory (IL-10 and TGFβ) cytokines. Moreover, TB antigen stimulated whole blood also showed increased levels of pro-inflammatory (IFNγ, TNFα and IL-1β) cytokines as well. However, the cytokines did not exhibit any significant correlation with HbA1C levels or with bacterial burdens.Conclusion
Our data reveal that pre-diabetes in PTB individuals is characterized by heightened cytokine responsiveness, indicating that a balanced pro and anti - inflammatory cytokine milieu is a feature of pre-diabetes - TB co-morbidity. 相似文献12.
Jonah Lin Ryan Law Chapin S. Korosec Christine Zhou Wan Hon Koh Mohammad Sajjad Ghaemi Philip Samaan Hsu Kiang Ooi Vitaliy Matveev FengYun Yue Anne-Claude Gingras Antonio Estacio Megan Buchholz Patti Lou Cheatley Avid Mohammadi Rupert Kaul Katerina Pavinski Samira Mubareka Allison J. McGeer Jerome A. Leis Jane M. Heffernan Mario Ostrowski 《Journal of virology》2022,96(13)
13.
Lynne R. Prince Nicola C. Maxwell Sharonjit K. Gill David H. Dockrell Ian Sabroe Eamon P. McGreal Sailesh Kotecha Moira K. Whyte 《PloS one》2014,9(8)
Background
The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation.Objectives
To investigate airway innate immune cellular phenotypes in preterm infants with respiratory distress syndrome (RDS) or CLD.Methods
Bronchoalveolar lavage (BAL) fluid was obtained from term and preterm infants requiring mechanical ventilation. BAL cells were phenotyped by flow cytometry.Results
Preterm birth was associated with an increase in the proportion of non-classical CD14+/CD16+ monocytes on the day of delivery (58.9±5.8% of total mononuclear cells in preterm vs 33.0±6.1% in term infants, p = 0.02). Infants with RDS were born with significantly more CD36+ macrophages compared with the CLD group (70.3±5.3% in RDS vs 37.6±8.9% in control, p = 0.02). At day 3, infants born at a low gestational age are more likely to have greater numbers of CD14+ mononuclear phagocytes in the airway (p = 0.03), but fewer of these cells are functionally polarized as assessed by HLA-DR (p = 0.05) or CD36 (p = 0.05) positivity, suggesting increased recruitment of monocytes or a failure to mature these cells in the lung.Conclusions
These findings suggest that macrophage polarization may be affected by gestational maturity, that more immature macrophage phenotypes may be associated with the progression of RDS to CLD and that phenotyping mononuclear cells in BAL could predict disease outcome. 相似文献14.
David Risco Emmanuel Serrano Pedro Fernández-Llario Jesús M. Cuesta Pilar Gon?alves Waldo L. García-Jiménez Remigio Martínez Rosario Cerrato Roser Velarde Luis Gómez Joaquím Segalés Javier Hermoso de Mendoza 《PloS one》2014,9(10)
Co-infections with parasites or viruses drive tuberculosis dynamics in humans, but little is known about their effects in other non-human hosts. This work aims to investigate the relationship between Mycobacterium bovis infection and other pathogens in wild boar (Sus scrofa), a recognized reservoir of bovine tuberculosis (bTB) in Mediterranean ecosystems. For this purpose, it has been assessed whether contacts with common concomitant pathogens are associated with the development of severe bTB lesions in 165 wild boar from mid-western Spain. The presence of bTB lesions affecting only one anatomic location (cervical lymph nodes), or more severe patterns affecting more than one location (mainly cervical lymph nodes and lungs), was assessed in infected animals. In addition, the existence of contacts with other pathogens such as porcine circovirus type 2 (PCV2), Aujeszky''s disease virus (ADV), swine influenza virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and Metastrongylus spp, was evaluated by means of serological, microbiological and parasitological techniques. The existence of contacts with a structured community of pathogens in wild boar infected by M. bovis was statistically investigated by null models. Association between this community of pathogens and bTB severity was examined using a Partial Least Squares regression approach. Results showed that adult wild boar infected by M. bovis had contacted with some specific, non-random pathogen combinations. Contact with PCV2, ADV and infection by Metastrongylus spp, was positively correlated to tuberculosis severity. Therefore, measures against these concomitant pathogens such as vaccination or deworming, might be useful in tuberculosis control programmes in the wild boar. However, given the unexpected consequences of altering any community of organisms, further research should evaluate the impact of such measures under controlled conditions. Furthermore, more research including other important pathogens, such as gastro-intestinal nematodes, will be necessary to complete this picture. 相似文献
15.
链霉素耐药结核分支杆菌rpsL基因分析 总被引:6,自引:0,他引:6
结核分支杆菌(Mycobacterium tuberculosis.TB)的rpsL基因突变往往与链霉素(Streptomycin.SM)耐药变异有关。选择了77例TB临床分离株,应用BACTEC460快速培养系统进行常规药敏实验,同时针对rpsL基因进行聚合酶链反应(PCR),对PCR产物进行单链构型多态性(SSCP)分析,MboⅡ酶切后的限制性片段长度分析(RFLP)和序列测定分析。常规药敏实验显示:有20株为SM敏感,57株为耐药。SSCP显示:34株的rpsL基因为野生型,43株为突变型。与常规药敏相比SSCP的特异性与阳性预期值分别为95%和98%。RFLP显示:81.4%的突变类型使其失去MboⅡ酶切位点。序列测定显示:失去MboⅡ酶切位点的突变为rpsL基因43位密码子存有单碱基突变(AAG→AGG)。实验结果表明,TB对SM耐药变异与rpsL基因突变相关,其中第43位密码子的突变是最常见的原因。 相似文献
16.
Anon Srikiatkhachorn Sineewanlaya Wichit Robert V. Gibbons Sharone Green Daniel H. Libraty Timothy P. Endy Francis A. Ennis Siripen Kalayanarooj Alan L. Rothman 《PloS one》2012,7(12)
Background
Infection with dengue viruses (DENV) causes a wide range of manifestations from asymptomatic infection to a febrile illness called dengue fever (DF), to dengue hemorrhagic fever (DHF). The in vivo targets of DENV and the relation between the viral burden in these cells and disease severity are not known.Method
The levels of positive and negative strand viral RNA in peripheral blood monocytes, T/NK cells, and B cells and in plasma of DF and DHF cases were measured by quantitative RT-PCR.Results
Positive strand viral RNA was detected in monocytes, T/NK cells and B cells with the highest amounts found in B cells. Viral RNA levels in CD14+ cells and plasma were significantly higher in DHF compared to DF, and in cases with a secondary infection compared to those undergoing a primary infection. The distribution of viral RNA among cell subpopulations was similar in DF and DHF cases. Small amounts of negative strand RNA were found in a few cases only. The severity of plasma leakage correlated with viral RNA levels in plasma and in CD14+ cells.Conclusions
B cells were the principal cells containing DENV RNA in peripheral blood, but overall there was little active DENV RNA replication detectable in peripheral blood mononuclear cells (PBMC). Secondary infection and DHF were associated with higher viral burden in PBMC populations, especially CD14+ monocytes, suggesting that viral infection of these cells may be involved in disease pathogenesis. 相似文献17.
Jasna Martinovic Andrew Jones Paul Christiansen Abigail K. Rose Lee Hogarth Matt Field 《PloS one》2014,9(4)
Pavlovian to Instrumental Transfer (PIT) refers to the behavioral phenomenon of increased instrumental responding for a reinforcer when in the presence of Pavlovian conditioned stimuli that were separately paired with that reinforcer. PIT effects may play an important role in substance use disorders, but little is known about the brain mechanisms that underlie these effects in alcohol consumers. We report behavioral and electroencephalographic (EEG) data from a group of social drinkers (n = 31) who performed a PIT task in which they chose between two instrumental responses in pursuit of beer and chocolate reinforcers while their EEG reactivity to beer, chocolate and neutral pictorial cues was recorded. We examined two markers of the motivational salience of the pictures: the P300 and slow wave event-related potentials (ERPs). Results demonstrated a behavioral PIT effect: responding for beer was increased when a beer picture was presented. Analyses of ERP amplitudes demonstrated significantly larger slow potentials evoked by beer cues at various electrode clusters. Contrary to hypotheses, there were no significant correlations between behavioral PIT effects, electrophysiological reactivity to the cues, and individual differences in drinking behaviour. Our findings are the first to demonstrate a PIT effect for beer, accompanied by increased slow potentials in response to beer cues, in social drinkers. The lack of relationship between behavioral and EEG measures, and between these measures and individual differences in drinking behaviour may be attributed to methodological features of the PIT task and to characteristics of our sample. 相似文献
18.
Marcio Roberto Silva Adalgiza da Silva Rocha Ronaldo Rodrigues da Costa Andrea Padilha de Alencar Vania Maria de Oliveira Ant?nio Augusto Fonseca Júnior Mariana Lázaro Sales Marina de Azevedo Issa Paulo Martins Soares Filho Omara Tereza Vianello Pereira Eduardo Calazans dos Santos Rejane Silva Mendes ?ngela Maria de Jesus Ferreira Pedro Moacyr Pinto Coelho Mota Philip Noel Suffys Mark Drew Crosland Guimar?es 《Memórias do Instituto Oswaldo Cruz》2013,108(3):321-327
In this cross-sectional study, mycobacteria specimens from 189 tuberculosis (TB) patients living in an urban area in Brazil were characterised from 2008-2010 using phenotypic and molecular speciation methods (pncA gene and oxyR pseudogene analysis). Of these samples, 174 isolates simultaneously grew on Löwenstein-Jensen (LJ) and Stonebrink (SB)-containing media and presented phenotypic and molecular profiles of Mycobacterium tuberculosis, whereas 12 had molecular profiles of M. tuberculosis based on the DNA analysis of formalin-fixed paraffin wax-embedded tissue samples (paraffin blocks). One patient produced two sputum isolates, the first of which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, and the second of which only grew on SB media and presented phenotypic profiles of Mycobacterium bovis. One patient provided a bronchial lavage isolate, which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, but had molecular profiles of M. bovis from paraffin block DNA analysis, and one sample had molecular profiles of M. tuberculosis and M. bovis identified from two distinct paraffin blocks. Moreover, we found a low prevalence (1.6%) of M. bovis among these isolates, which suggests that local health service procedures likely underestimate its real frequency and that it deserves more attention from public health officials. 相似文献
19.
Margaret E. Ackerman Anastassia Mikhailova Eric P. Brown Karen G. Dowell Bruce D. Walker Chris Bailey-Kellogg Todd J. Suscovich Galit Alter 《PLoS pathogens》2016,12(1)
Elite controllers (ECs) represent a unique model of a functional cure for HIV-1 infection as these individuals develop HIV-specific immunity able to persistently suppress viremia. Because accumulating evidence suggests that HIV controllers generate antibodies with enhanced capacity to drive antibody-dependent cellular cytotoxicity (ADCC) that may contribute to viral containment, we profiled an array of extra-neutralizing antibody effector functions across HIV-infected populations with varying degrees of viral control to define the characteristics of antibodies associated with spontaneous control. While neither the overall magnitude of antibody titer nor individual effector functions were increased in ECs, a more functionally coordinated innate immune–recruiting response was observed. Specifically, ECs demonstrated polyfunctional humoral immune responses able to coordinately recruit ADCC, other NK functions, monocyte and neutrophil phagocytosis, and complement. This functionally coordinated response was associated with qualitatively superior IgG3/IgG1 responses, whereas HIV-specific IgG2/IgG4 responses, prevalent among viremic subjects, were associated with poorer overall antibody activity. Rather than linking viral control to any single activity, this study highlights the critical nature of functionally coordinated antibodies in HIV control and associates this polyfunctionality with preferential induction of potent antibody subclasses, supporting coordinated antibody activity as a goal in strategies directed at an HIV-1 functional cure. 相似文献
20.
JA Shah JC Vary TT Chau ND Bang NT Yen JJ Farrar SJ Dunstan TR Hawn 《Journal of immunology (Baltimore, Md. : 1950)》2012,189(4):1737-1746
Tuberculosis, one of the leading causes of death worldwide, stimulates inflammatory responses with beneficial and pathologic consequences. The regulation and nature of an optimal inflammatory response to Mycobacterium tuberculosis remains poorly understood in humans. Insight into mechanisms of negative regulation of the TLR-mediated innate immune response to M. tuberculosis could provide significant breakthroughs in the design of new vaccines and drugs. We hypothesized that TOLLIP and its common variants negatively regulate TLR signaling in human monocytes and are associated with susceptibility to tuberculosis. Using short hairpin RNA knockdown of TOLLIP in peripheral blood human monocytes, we found that TOLLIP suppresses TNF and IL-6 production after stimulation with TLR2 and TLR4 ligands. In contrast, secretion of the anti-inflammatory cytokine IL-10 was induced by TOLLIP. We also discovered two common polymorphisms that are associated with either decreased levels of mRNA expression (rs3750920) or increased IL-6 production (rs5743899) in a sample of 56 healthy volunteers. Furthermore, in a case-population study in Vietnam with 760 cord blood samples and 671 TB case patients, we found that SNPs rs3750920 and rs5743899 were associated with susceptibility to tuberculosis (p = 7.03 × 10(-16) and 6.97 × 10(-7), respectively). These data demonstrate that TOLLIP has an anti-inflammatory effect on TLR signaling in humans and that TOLLIP deficiency is associated with an increased risk of tuberculosis. To our knowledge, these data also show the first associations of TOLLIP polymorphisms with any infectious disease. These data also implicate an unexpected mechanism of negative regulation of TLR signaling in human tuberculosis pathogenesis. 相似文献